In the field of immunology, it is often necessary that more than one dose of an antigen be administered for producing an immunological response in an animal sufficient to ward off an impeding infection. Similar regimes have been advocated and used as an immunological program in the management of a disease in progress. In practice, multiple doses are administered because repeated interaction of immune system cells with antigen and necessary to build up the systems immune response. Further, multiple doses are required because the antigen is cleared from the site of administration or degraded by the animal too rapidly for permitting interaction between the cells and the antigen.
The prior art was attempted to increase both the persistence of the antigen and the vigor of the immune response, and avoid the use of multiple doses by administering an adjuvant with the antigen. The adjuvants used for the purpose consist of (a) substances like kaolin, gum tragacanth, tapioca, alum, aluminum hydroxide, calcium chloride and sodium alginate, oils and emulsions, which act as a depot for the antigens, as well as (b) substances like inactivated or attenuated bacteria, lipopolysaccharides, mucopeptides, other bacterial products possessing adjuvant properties, saponin, and synthetic organic compounds which potentiate the immune response by regulating active cell behavior. While the development and the use of adjuvants and depots represent a contribution to the prior art, serious disadvantages are associated with their use. For example, while one of the aims of using an immunologic adjuvant is to achieve a more durable immunity of a higher level than is obtained with a single dose of the antigen, in many instances a number of doses still are required to produce this intended result. In many instances the level of immunity achievable in a short time interval, for example seven to fourteen days, and it is inadequate for protecting from immediate threatening infections. In most instances the adjuvants themselves are a source of irritation that leads to severe inflammation. The prior art method of administration also exposes an unknown amount of both antigen and adjuvant, the latter often having adverse properties, to direct contact with local tissue; with the resulting duration and severity of the ensuing inflammatory response being therefore highly variable. Also, it is not known to the prior art that such materials could be administered and be effective in low amounts delivered at a controlled rate and continuously over a prolonged period of time. Currently, the use of depots, which are intended to function as an in vivo repository for an antigen, is replete with shortcomings. That is, depots do not keep their integrity and accordingly they do not maintain a predictable repository effect. By losing their integrity, they allow large numbers of inflammatory cells to accumulate at the depot site thereby producing unwanted irritation and often granulomatous lesions. Depots previously known to the art are made of materials that spread and diffuse throughout the area in which they are injected and they are not conducive for the controlled release of antigens over time. Also, depots are not immunopotentiators as they merely supply an antigen and they do not stimulate T-cells, B-cells, NK-cells, and the like.
It will be appreciated by those versed in the art and from the above presentation that if a method is made available for delivering an antigen and immunopotentiator to enhance the immune response, which method is essentially free of the disadvantages of multiple doses and the disadvantages of depots as known to the prior art, such a method would represent a valuable contribution to the art. Likewise, it will be appreciated by those versed in the art that if a method is made available which avoids giving rise to significant local inflammation and the like, such a method also would be a useful contribution to the art. Similarly, it will be appreciated that if a method is provided which accelerates the appearance of the immune response at protective levels, such a method would also be an improvement in the art.